Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00443976

Collaborator

Astex Pharmaceuticals, Inc. (Industry)

Enrollment

Locations

Arm

60.1

Actual Duration (Months)

17.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Aurora kinase inhibitor AT9283 (AT9283) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of AT9283 in treating patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkins Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: Aurora kinase inhibitor AT9283	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose and recommended phase II dose of Aurora kinase inhibitor AT9283 (AT9283) in patients with incurable advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
Determine the safety, tolerability, toxicity profile, dose-limiting toxicity, and pharmacokinetic profile of this drug in these patients.
Correlate the toxicity profile with the pharmacokinetics of this drug in these patients.
Assess, preliminarily, evidence of antitumor activity of this drug in these patients.
Determine the pharmacodynamic activity of this drug in these patients and correlate with biological endpoints.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive Aurora kinase inhibitor AT9283 (AT9283) IV over 24 hours on days 1 and 8 . Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AT9283 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The dose preceding the MTD is the recommended phase II dose (RPTD). Up to 8 additional patients are treated at the RPTD.

Patients treated at the RPTD undergo skin and tumor tissue biopsy and blood collection at baseline and on days 2 and/or 3. Samples are examined by pharmacokinetic and pharmacodynamic analysis, including immunohistochemistry, immunocytochemistry, western blotting, immunoenzyme techniques, flow cytometry, and reverse transcriptase-polymerase chain reaction, for biological markers.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months until disease progression.

PROJECTED ACCRUAL: Up to 30 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of AT9283 Given As a 24 Hour Infusion on Days 1 and 8 Every Three Weeks in Patients With Advanced Incurable Malignancy

Actual Study Start Date :

Jan 4, 2007

Actual Primary Completion Date :

Apr 9, 2010

Actual Study Completion Date :

Jan 6, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AT9283	Drug: Aurora kinase inhibitor AT9283 The starting dose of AT9283 will be 1.5 mg/m2 given as a 24 hour IV infusion on Days 1 and 8 every three weeks.

Arm

Intervention/Treatment

Experimental: AT9283

Drug: Aurora kinase inhibitor AT9283

The starting dose of AT9283 will be 1.5 mg/m2 given as a 24 hour IV infusion on Days 1 and 8 every three weeks.

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283) [1 year]
Doses escalated as described in protocol section 4.3. MTD defined as that dose at which ≥ 2/6 or ≥ 2/3 patients experience DLT (as defined in protocol section 4.4).
Recommended phase II dose of AT9283 [1 year]
RPTD defined as one dose lower than MTD.
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283 [every 3 weeks]
Adverse events graded using NCI CTCAE V3.0
Pharmacokinetic profile of AT9283 [cycle one only]
PK samples collected on all patients during cycle 1 as described in protocol section 17.2.

Secondary Outcome Measures

Efficacy of AT9283 [every 6 weeks]
All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed diagnosis of 1 of the following:
Advanced and/or metastatic solid tumor
Advanced or metastatic non-Hodgkin's lymphoma refractory to standard therapy
Clinically or radiologically documented disease
No tumor marker elevation as only evidence of disease
No untreated brain or meningeal metastases
Treated and stable brain metastases allowed provided they are asymptomatic and do not require steroids

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.25 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
Bilirubin normal
ALT and AST ≤ 2 times ULN (≤5 times ULN if liver metastases are present)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use two effective methods of contraception
No untreated or uncontrolled hypertension, cardiovascular conditions, or symptomatic cardiac dysfunction
No active or uncontrolled infections
No serious illness or medical condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

At least 2 weeks since prior major surgery and recovered
At least 3 weeks since prior palliative radiotherapy and recovered
Low-dose, nonmyelosuppressive radiotherapy may be allowed
At least 3 weeks since prior chemotherapy for solid tumors and recovered
No more than 2 prior cytotoxic chemotherapy regimens for metastatic disease
At least 4 weeks since prior steroids
No limitations on prior therapy for patients with non-Hodgkin's lymphoma
Prior hormonal, immunologic, biologic or signal transduction inhibitor therapy allowed
No other concurrent investigational agents
No other concurrent anticancer therapy